Role of methionine containing antioxidant combination in the management of pain in chronic pancreatitis: A systematic review and meta-analysis

Background: Pain in CP results from inflammation and neuroimmune alterations that are associated with oxidative stress, among other mechanisms. This is marked by depletion of antioxidant defenses including methionine, which is a donor of methyl moieties that maintains the acinar transsulfuration pathway. We performed a systematic review and meta-analysis of trials evaluating methionine-containing antioxidants in CP. Patient and methods: Literature search was conducted in Medline/Pubmed, EMBASE, and Cochrane databases. Systematic review and meta-analysis was performed per PRISMA guidelines. Main study outcome was pain relief. GRADE system was used for quality assessment. Heterogeneity was assessed by the Q and I-2 measures; publication bias by Eggers test. Random-effect model (DerSimonian and Laird) was used if there was heterogeneity. Results: Eight studies (n = 411) were identified that used methionine-containing antioxidants. The study duration ranged from 10 wks to 12 months. All studies used methionine, organic selenium, ascorbate, beta-carotene and alpha-tocoferol. Four studies (including two RCTs) that reported change in pain scores were metaanalyzed. Though overall effect [standardized difference in means (95% CI)] on pain score reduction was -0.95 (-1.738 to -0.160) (z = -236; p = 0.018), the significance was lost when the two RCTs were meta-analyzed. RCTs that reported the number of pain free patients had a statistically significant overall effect of -3.204 (p = 0.001). Though more patients on methionine containing antioxidants had adverse events, majority of them were mild. Conclusion: Methionine containing antioxidants appear to result in pain reduction in a significant proportion of CP patients. Further randomized controlled trials with homogeneous outcome measures are needed. Copyright (C) 2015, IAP and EPC. Published by Elsevier India, a division of Reed Elsevier India Pvt. Ltd. All rights reserved.